Congenital hyperinsulinism (HI) is a challenging disorder causing hypoglycemia in newborns and children for which current therapy is inadequate. It is imperative to develop new therapeutic approaches for the care of patients with HI. One such agent is insulin-like growth factor-I (IGF-I) which has been demonstrated to be a potent inhibitor of insulin secretion in several conditions. Therapy with IGF-I has been shown to decrease insulin secretion in normal volunteers, in patients with insulin-resistance syndromes, and in patients with growth hormones receptor deficiency. Based on these findings, we thereby ameliorate the fasting hypoglycemia associated with congenital hyperinsulinism. The specific aims of this study are: 1) to confirm the inhibitory effect of IGF-I on insulin secretion in the hyperinsulinism population; 2) to define the effects of short term IGF-I therapy on post-prandial blood sugar levels in children with hyperinsulinism; 3) to characterize the effects of short term IGF-I therapy on fasting behavior, and other insulin dependent parameters, in children with hyperinsulinism; 4) to conduct a study of IGF-I in patients with hyperinsulinism refractory to current medical management prior to surgical intervention; and 5) to evaluate the efficacy of longer term IGF-I treatment in children with hyperinsulinism in a randomized double-blind placebo-controlled cross-over study. So far we have demonstrated that IGF-I inhibits insulin secretion in patients with HI. We are still sorting out the dosing issues and the effects on glucose.